A-type nuclear lamins act as transcriptional repressors when targeted to promoters

Journal Article · Wed Apr 01 04:00:00 EDT 2009 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2009.01.003· OSTI ID:21176192

Lee, Damian C; Welton, K Linnea ^[1]; Smith, Erica D ^[1]

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1. Department of Biochemistry, University of Washington, Seattle, WA 98195 (United States)

Regions of heterochromatin are often found at the periphery of the mammalian nucleus, juxtaposed to the nuclear lamina. Genes in these regions are likely maintained in a transcriptionally silent state, although other locations at the nuclear periphery associated with nuclear pores are sites of active transcription. As primary components of the nuclear lamina, A- and B-type nuclear lamins are intermediate filament proteins that interact with DNA, histones and known transcriptional repressors, leading to speculation that they may promote establishment of repressive domains. However, no direct evidence of a role for nuclear lamins in transcriptional repression has been reported. Here we find that human lamin A, when expressed in yeast and cultured human cells as a fusion protein to the Gal4 DNA-binding domain (DBD), can mediate robust transcriptional repression of promoters with Gal4 binding sites. Full repression by lamin A requires both the coiled-coil rod domain and the C-terminal tail domain. In human cells, other intermediate filament proteins such as lamin B and vimentin are unable to confer robust repression as Gal4-DBD fusions, indicating that this property is specific to A-type nuclear lamins. These findings indicate that A-type lamins can promote transcriptional repression when in proximity of a promoter.

• OSTI ID: 21176192
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 6 Vol. 315; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
DNA
GENES
HETEROCHROMATIN
HISTONES
PROMOTERS
TRANSCRIPTION
YEASTS